资源类型

期刊论文 28

年份

2023 3

2022 1

2020 2

2019 2

2016 3

2015 1

2014 1

2013 2

2012 2

2011 1

2010 1

2009 6

2008 1

2007 2

展开 ︾

关键词

假单胞菌 1

富含异亮氨酸的延伸蛋白 1

环状脂肽 1

类受体激酶 1

细胞死亡 1

展开 ︾

检索范围：

排序： 展示方式：

Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

Fen LAN, Shengdao XIONG, Weining XIONG, Guopeng XU, Xiaoxia LU

《医学前沿（英文）》 2009年 第3卷 第1期   页码 41-44 doi: 10.1007/s11684-009-0009-6

摘要： This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinicopathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell cancer, 16 cases of lung adenocarcinoma) and tumor-surrounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumor-surrounding normal lung tissues, respectively. The expression level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues ( = 0.000). The Syk expression was positively correlated withthe p53 expression in NSCLC specimens ( = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.

关键词： Syk kinase     carcinoma     non-small-cell lung     tumor suppressor protein p53    

HTML PDF 收藏

The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 70-76 doi: 10.1007/s11684-011-0119-9

摘要：

Protein kinase C epsilon (PKC ?) is one of major isoforms in novel PKC family. Although it has been extensively characterized in the past decade, the role of PKC ? in neuron is still not well understood. Advances in molecular biology have now removed significant barriers to the direct investigation of PKC ? functions in vivo, and PKC ? has been increasingly implicated in the neural biological functions and associated neurogenic diseases. Recent studies have provided important insights into the influence of PKC ? on cortical processing at both the single cell level and network level. These studies provide compelling evidence that PKC ? could regulate distinct aspects of neural signal transduction and suggest that the coordinated actions of a number of molecular signals contribute to the specification and differentiation of PKC ? signal pathway in the developing brain.

关键词： protein kinase C ?     signal transduction     neurogenic disease    

HTML PDF 收藏

Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 383-388 doi: 10.1007/s11684-016-0488-1

摘要：

The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9–13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.

关键词： EGFR     tyrosine kinase inhibitor     AZD9291     EAI045    

HTML PDF 收藏

Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation

LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing

《医学前沿（英文）》 2008年 第2卷 第3期   页码 235-238 doi: 10.1007/s11684-008-0044-8

摘要： The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307) phosphorylation, protein phosphatase 2A (PP2A) activity, and on tau phosphorylation. Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein, and the phosphorylation levels of PP2A Y307 and tau at different sites, as well as PP2A activity were detected at different time points after siRNA transfection. Twelve hours after siRNA transfection, the protein level of Src was dramatically decreased, with decreased PP2A Y307 phosphorylation. However, the total PP2A protein level was also decreased, together with a decreased PP2A activity. Tau was hyperphosphorylated at the Ser198/199/202 sites. Multiple factors may be involved in the cellular regulation of PP2A activity. Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.

关键词： hyperphosphorylation     PP2A activity     cellular regulation     siRNA     siRNA transfection    

HTML PDF 收藏

Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventive

XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing

《医学前沿（英文）》 2007年 第1卷 第2期   页码 200-206 doi: 10.1007/s11684-007-0038-y

摘要： Elevated plasma levels of free fatty acids (FFAs) may contribute to insulin resistance (IR) that is characteristic of type 2 diabetes mellitus. In this study, we investigated the effects of two fatty acids, palmitate (PA) and arach

关键词： palmitate     characteristic     study     plasma     resistance    

HTML PDF 收藏

effects of ketamine with increased levels of brain-derived neurotrophic factor and tropomyosin-related kinase

null

《医学前沿（英文）》 2012年 第6卷 第4期   页码 411-415 doi: 10.1007/s11684-012-0226-2

摘要：

Ketamine exerts rapid and robust antidepressant properties in both animal models and depressed patients and tramadol possesses potential antidepressant effects. Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF. We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats. Immobility time of rats receiving different treatment in the forced swimming test (FST) was observed. Levels of BDNF and TrkB in hippocampus were measured by enzyme linked immunosorbent assay. Results showed that tramadol (5 mg/kg) administrated alone neither elicited antidepressant effects nor altered BDNF or TrkB level. However, pretreatment with tramadol (5 mg/kg) enhanced the ketamine (10 mg/kg) -elicited antidepressant effects and upregulated the BDNF and TrkB levels in hippocampus. In conclusion, tramadol pretreatment reinforces the ketamine-elicited antidepressant effects, which is associated with the increased levels of BDNF and TrkB in rat hippocampus.

关键词： tramadol     ketamine     antidepressant     brain-derived neurotrophic factor     tropomyosin-related kinase B    

HTML PDF 收藏

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 134-138 doi: 10.1007/s11684-015-0396-9

摘要：

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

关键词： targeted therapy     drug resistance     receptor tyrosine kinases     cancer    

HTML PDF 收藏

Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 46-53 doi: 10.1007/s11684-010-0010-0

摘要： Mitogen-activated protein kinase (MAPK) signaling pathway, one of the most important signaling pathways in eukaryotic organism, is involved in multiple cellular events such as cell growth, differentiation, and apoptosis. MAPK is of great importance to the normal function of organisms, while its dysfunction results in various diseases. So far, inhibitors specifically against each subfamilies of MAP kinase have been developed, while more endeavors are needed to discover the compounds selectively targeting a particular subfamily member. Most of the kinase inhibitors exert their functions in an ATP-competitive way or a non-ATP-competitive way. Further studies on the effective mechanism of the MAPK inhibitors and their therapeutic roles in the treatment of diseases are helpful for the illumination of MAP kinase function, the development of novel inhibitors, and the therapy of diseases caused by the dysfunction of the MAPK pathway.

关键词： mitogen-activated protein kinase     drug target     inhibitor     signal transduction     disease    

HTML PDF 收藏

Protective effect of tanshinone II A on signal transduction system protein kinase B in rats with myocardial

Enyuan TU MD, Yongjun PAN MM, Kang ZHENG MM, Zhaohua WANG MD, Qiansheng LIANG MD, Guangtian YANG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 431-436 doi: 10.1007/s11684-009-0088-4

摘要： The effects of tanshinone II A on cell signal transduction system protein kinase B in rats with myocardial hypertrophy induced by the abdominal aorta partial coarctation were investigated. Rat models of myocardial hypertrophy were established by using abdominal aorta partial coarctation method. Forty-eight rats were randomly divided into sham group (S group), model group (M group), valsartan treatment group (X group), low-dose tanshinone treatment group (LD group), medium-dose tanshinone treatment group (MD group), and high-dose tanshinone treatment group (HD group) (=8 in each group). Left ventricular mass index (LVMI), left ventricular posterior wall (LVPW), and septal thickness (IVS) were detected by high frequency ultrasonography. Myocardial fiber diameter (MFD) was examined by Hematoxylin-Eosin (HE) staining, and the contents of phosphorylated protein kinase B (p-Akt) and p-Gsk3β in myocardium were assayed by Western blot. The results showed that compared with S group, the values of LVMI, LVPW, IVS and MFD were increased in other groups (<0.05), and the contents of p-Akt, and p-Gsk3β were also increased in other groups. As compared with MD group, the values of LVMI, LVPW, IVS and MFD were decreased in all treatment groups (<0.05), and the contents of p-Akt, and p-Gsk3β were also decreased in all treatment groups. However, there were no significant differences among LD, MD, and HD groups (>0.05), and there were no significant differences between X group and tanshinone treatment groups (>0.05). It was suggested that tanshinone II A could prevent myocardial hypertrophy by its action on the Akt signaling pathway.

关键词： tanshinone II A     myocardial hypertrophy     rat     protein kinase B     abdominal aorta coarctation    

HTML PDF 收藏

Effects of phosphatidylinositol 3-kinase inhibitor on human cervical carcinoma cells

Yuan ZHANG MD , Xiaoyan ZHANG MM , Yanhui LI MM , Xuan DU MM , Zehua WANG MD, PhD , Hongbo WANG MD ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 341-346 doi: 10.1007/s11684-009-0067-9

摘要： Phosphatidylinositol 3-kinase (PI3K) is a crucial cell survival pathway implicated in tumorigenesis because of its role in stimulating cell proliferation and suppressing apoptosis. This study was to investigate the regulation of proliferation and apoptosis by LY294002, an inhibitor of PI3K in cervical cancer cells and the expression of FLICE-like inhibitory protein (c-FLIP) . Human cervical cancer HeLa cells were used in this experiment and cultured. The cultured cells were treated with LY294002 at different concentrations (10, 25, 50 and 100µmol/L) for 6, 12, 24, and 48h before harvesting for evaluation. Cell viability was measured by 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide (MTT) assay. Apoptosis was analyzed by flow cytometry. The expression of c-FLIP was detected by Western blot. Cell viability was inhibited by LY294002 significantly (<0.05). Flow cytometry analysis revealed that cell apoptosis was significantly increased in the presence of LY294002 as compared with the control group. Although the expression of c-FLIP was increased in a short time, the expression of c-FLIP was markedly suppressed after the treatment of LY294002 for 48h. These results suggested that the PI3K/Akt signal pathway might be involved in the regulation of cell apoptosis in cervical cancer cells. Moreover, the regulation of c-FLIP expression through PI3K/Akt signal pathway in cervical cancer cells was observed .

关键词： human cervical cancer cells     apoptosis     phosphatidylinositol 3-kinase (PI3K)/Akt     FLICE-like inhibitory protein    

HTML PDF 收藏

Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 481-489 doi: 10.1007/s11684-016-0494-3

摘要：

The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity (PCP) of hair cells. LKB1 deficiency in LKB1Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.

关键词： LKB1     stereociliary bundles     kinocilium     planar cell polarity     hearing     mice    

HTML PDF 收藏

Involvement of p38 mitogen-activated protein kinase in the regulation of platelet-derived growth factor

GONG Xiaowei, WEI Jie, LI Yusheng, CHENG Weiwei, DENG Peng, JIANG Yong

《医学前沿（英文）》 2007年 第1卷 第3期   页码 248-252 doi: 10.1007/s11684-007-0047-x

摘要： The aim of this study was to investigate the role of p38 mitogen-activated protein kinase (MAPK) in cell migration induced by platelet-derived growth factor (PDGF). Western blot was performed to detect the phosphorylation of p38 in NIH3T3 cells treated with PDGF. A Transwell cell migration system was used to determine the effects of PDGF treatment on the migration of NIH3T3 cells and the influence of deficiency on this process in a gene knockout (p38) mouse embryonic fibroblast cell line. On the stimulation of PDGF, the migration of NIH3T3 cells was significantly increased (〈0.001) compared to the control and p38 MAP kinase was simultaneously phosphorylated. Furthermore, the PDGF-induced cell migration was significantly blocked in gene knockout (p38) mouse embryonic fibroblasts (MEFs) (〈0.001) as compared with the wild type cells (p38). p38 MAPK plays an important role in the regulation of cell migration induced by PDGF.

关键词： control     stimulation     mitogen-activated     growth factor     process    

HTML PDF 收藏

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

《医学前沿（英文）》 2023年 第17卷 第2期   页码 290-303 doi: 10.1007/s11684-022-0956-8

摘要： Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine     cyclin-dependent kinase 2     patient-derived xenograft     esophageal squamous cell carcinoma    

HTML PDF 收藏

Mechanisms of insulin resistance in obesity

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 14-24 doi: 10.1007/s11684-013-0262-6

摘要：

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that, there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.

关键词： type 2 diabetes     energy expenditure     inflammation     lipotoxicity     mitochondria     hyperinsulinemia     adenosine monophosphate-activated protein kinase (AMPK)    

HTML PDF 收藏

breast cancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinase

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 186-195 doi: 10.1007/s11705-015-1540-4

摘要： Increased expression levels of the RNA splicing regulator Transformer2 (abbreviated Tra2 ) have been reported in several types of cancer. Recent work has revealed an intimate cross-regulation between Tra2 and the highly similar Tra2 protein in human breast cancer cells, though these two proteins are encoded by separate genes created by a gene duplication that occurred over 500 million years ago. This cross-regulation involves splicing control of a special class of exons, called poison exons. Down-regulation of Tra2 reduces splicing inclusion of a poison exon in the mRNA encoding Tra2 , thereby up-regulating Tra2 protein expression. This buffers any splicing changes that might be caused by individual depletion of Tra2 alone. Discovery of this cross-regulation pathway, and its by-pass by joint depletion of both human Tra2 proteins, revealed Tra2 proteins are essential for breast cancer cell viability, and led to the identification of important targets for splicing control. These exons include a critical exon within the checkpoint kinase 1 (CHK1) gene that plays a crucial function in the protection of cancer cells from replication stress. Breast cancer cells depleted for Tra2 proteins have reduced CHK1 protein levels and accumulate DNA damage. These data suggest Tra2 proteins and/or their splicing targets as possible cancer drug targets.

关键词： RNA splicing     gene expression     breast cancer     DNA damage     CHK1    

HTML PDF 收藏

标题 作者 时间 类型 操作

Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

Fen LAN, Shengdao XIONG, Weining XIONG, Guopeng XU, Xiaoxia LU

期刊论文

The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

null

期刊论文

Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

null

期刊论文

Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation

LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing

期刊论文

Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventive

XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing

期刊论文

effects of ketamine with increased levels of brain-derived neurotrophic factor and tropomyosin-related kinase

null

期刊论文

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

期刊论文

Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

期刊论文

Protective effect of tanshinone II A on signal transduction system protein kinase B in rats with myocardial

Enyuan TU MD, Yongjun PAN MM, Kang ZHENG MM, Zhaohua WANG MD, Qiansheng LIANG MD, Guangtian YANG MD,

期刊论文

Effects of phosphatidylinositol 3-kinase inhibitor on human cervical carcinoma cells

Yuan ZHANG MD , Xiaoyan ZHANG MM , Yanhui LI MM , Xuan DU MM , Zehua WANG MD, PhD , Hongbo WANG MD ,

期刊论文

Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

期刊论文

Involvement of p38 mitogen-activated protein kinase in the regulation of platelet-derived growth factor

GONG Xiaowei, WEI Jie, LI Yusheng, CHENG Weiwei, DENG Peng, JIANG Yong

期刊论文

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

期刊论文

Mechanisms of insulin resistance in obesity

null

期刊论文

breast cancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinase

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

期刊论文